Qualifying a human Liver-Chip for predictive toxicology: Performance assessment and economic implications

Human organ-on-a-chip (Organ-Chip) technology has the potential to disrupt preclinical drug dis-covery and improve success in drug development pipelines as it can recapitulate organ-level patho-physiology and clinical responses. The Innovation and Quality (IQ) consortium formed by multiple pharmaceutical and biotechnology companies, however, systematic and quantitative evaluation of the predictive value of Organ-Chips has not yet been reported. Here, 780 Liver-Chips were analyzed to determine their ability to predict drug-induced liver injury (DILI) caused by small molecules identified as benchmarks by the IQ consortium. The Liver-Chip met the qualification guidelines across a blinded set of 27 known hepatotoxic and non-toxic drugs with a sensitivity of 80% and a specificity of 100%. With this performance, a computational economic value analysis suggests that the Liver-Chip could generate $3 billion annually for the pharmaceutical industry due to increased R&D productivity.